By Giuliana Miglierini
The implementation process of the revised Certificates of suitability to the EU Pharmacopeia (CEP 2.0) is marking a new step, as announced by the European Directorate for the Quality of Medicines & HealthCare (EDQM).
Starting on 1 June 2023, it will be mandatory to provide, in the application forms for new dossiers, sister files and revisions and renewals, the EMA SPOR/OMS ORG_ID and LOC_ID for all companies involved in CEP dossiers. According to the Directorate, revised application forms for CEP submissions will also soon be available.
The process to redesign CEPs started in late 2020 with a public consultation, followed by a second, more targeted one in 2022. Received comments have supported the shaping of new CEPs by the Certification Steering Committee; CEPs 2.0 are expected to entry into force in 2023.
All changes made in the nine areas related to CEP’s submission and processing are detailed in a document available at the EDQM website. These include among others the assessment of CEP applications, on-line public certification and authorities’ databases, information sharing between CEP holders and marketing authorisation holders, the reduction of revisions, the assessment of the impact of changes and their implementation, training for both CEP holders and users, and the revision of documents available on the EDQM website.
The new mandatory data
ORG_ID and LOC_ID are unique identifiers for, respectively, an organisation and its locations. CEPs 2.0 will mention these details together with the company name and address in order to support a better identification of the specific facility involved in the manufacturing process.
The EDQM’s suggestion is to obtain as soon as possible an ORG_ID and LOC_ID, as these data will be requested for ongoing submissions during the evaluation of the dossier. The responsibility to assign the two identifiers falls under the European Medicines Agency (EMA), and it is managed through the SPOR/OMS database. All information needed to request the identifiers is available at the dedicated page on EMA’s website.
The EDQM has also launched a public consultation on the draft template of the letter of access deemed to replace the declaration of access box on the CEP document. The consultation will remain open until 16 April 2023, and it can be accessed from the consultation space of the EDQM’s website.
Insights of the new CEP 2.0
CEP 2.0 will be a digitally signed electronic document, that applicants for a marketing authorisation need to include in the authorisation dossier. CEP holders can choose to print it or share it with their customers in the pdf format.
The undergoing revision of the CEP’s renewal procedure will lead to a change in the numbering of the certificates. As mentioned above, the previous declaration of access box will be replaced by a letter of access, and ORG_ID and LOC_ID validated organisation data will become mandatory for all CEPs’ applications.
CEP’s contents will also be revised, with respect to the information provided for chemical purity, Herbal Drug/Herbal Drug preparations and related to the quality of the substance.
A new appendix detailing the specification applied by the CEP holder and the additional methods to control the quality of the substance approved during the assessment of the CEP dossier will replace the section on “Technical” information (e.g. additional controls for impurities or solvents). CEP 2.0 will also contain information on the quality of water used in the last steps of the synthesis of the substance.
Under the new framework, the CEP dossier, the assessment performed, and the approved specifications will be fully aligned. This means that unapproved information shall be excluded from the dossier. For example, process description and specifications should refer only to information corresponding to the claimed quality. Inclusion of stability data in CEP applications will be encouraged, also with reference to additional climatic zones.
CEPs 2.0 will be available through the public CEP database on the EDQM website. The information provided will include ORG-ID and LOC_ID identifiers and the history of the finalised procedures for each CEP application, so to make available a more transparent source of information but avoiding any reference to the exact changes introduced in the CEP dossier.
The revision of CEP 2.0 is expected to run more smoothly, as only changes impacting on CEP contents will lead to the issuing of a revised certificate. This means also that the numbering of CEPs will change, as it will be removed the part related to renewal.
Sharing of information with authorities and customers
Confidential information on the lifecycle of CEP applications, together with copies of the current CEPs and CEP assessment reports, will be available within a the separate Authorities database. Access to this database shall be granted to licensing authorities of the member states of the Ph. Eur. convention, in order to support the review of marketing applications for medicinal products where a CEP is included. This second database will also be enriched with the new information, including the two mandatory identifiers, CEP number and CEP document corresponding to each procedure of a dossier. Access may also be granted to regulatory authorities upon signature of confidentiality agreements or a Memorandum of Understanding.
Under the new CEP 2.0 framework, CEP applicants shall also commit to share information with their customers as part of the application form for a CEP. Not only a specific sentence will be added to the CEP document, but compliance will also be verified during inspections.
Steps in the implementation of CEP 2.0
The “new look” electronic CEPs will include all the above-mentioned innovation in contents, i.e. move of specifications and additional methods to an appendix, new numbering, SPOR/OMS LOC/ORG ID, letter of access, e-signature, etc. This type of document will be issued for any new CEP granted and after the renewal procedures (request of dossier integration is possible).
As for already existing CEPs, “hybrid look” certificates will be granted after approval of revision applications and notifications should the content be impacted, but without appending the company’s specifications. “Old look” CEPs refer to certificates granted before the implementation of CEP 2.0. These will maintain their validity until revision occurs.
The EDQM announced the publication of some training materials to facilitate users to navigate across the different types of CEPs. Webinars should also be organised in May 2023 to support the implementation of CEP 2.0.
The new framework will also impact on a series of other EDQM documents available under the “Certification policy documents and guidelines” section of the website. These will also undergo a progressive revision, and include among others applications forms, content of the dossier for chemical purity and microbiological quality, EDQM guideline on requirements for Revisions/Renewal of Certificates of Suitability to the EU Pharmacopoeia Monographs, etc.